Amir Sarayani1,2, Joshua D Brown1,2, Amie J Goodin1,2, Patrick Squires1,2, Phuong Pham1,2, Brian Cicali3, Carl Henriksen1, Stephan Schmidt3,4, Almut G Winterstein1,2. 1. From the Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, FL. 2. Center for Drug Evaluation and Safety, University of Florida, FL. 3. Department of Pharmaceutics, College of Pharmacy, University of Florida, FL. 4. Center for Pharmacometrics and Systems Pharmacology, University of Florida, FL.
Abstract
BACKGROUND: Accurate estimation of conception is critical in the assessment of the effects of drugs used during pregnancy or to prevent pregnancy. In a novel application, we studied the effectiveness of oral contraceptives (OCs), where misclassification of conception relative to OC exposure may obscure effect estimates. METHODS: We studied OC failure, in a large claims database, among women who used antiepileptic drugs with metabolizing enzyme-inducing properties (carbamazepine or oxcarbazepine), which reduce OC's effectiveness or enzyme-neutral properties (lamotrigine or levetiracetam), with no expected impact on OC effectiveness. We compared conception rates in women 12-48 years of age concomitantly using OCs and enzyme-inducing drugs with rates in concomitant users of OCs and enzyme-neutral drugs. We measured conception with a validated algorithm that estimates gestational age based on pregnancy endpoints. We estimated relative and attributable risk using generalized estimating equation models after standardized mortality ratio weighting. RESULTS: We identified 89,777 concomitant use episodes with adjusted contraceptive failure rates of 1.6 (95% confidence interval (CI) = 1.4, 1.8) per 100 person-years among users of enzyme-neutral drugs and 18,964 episodes with a rate of 2.3 (1.9, 2.8) among users of enzyme-inducing drugs. The relative risk of conception for enzyme-inducing group was 1.4 (1.1, 1.8), and the rate difference was 0.7 (0.2, 1.2). CONCLUSIONS: OCs in combination with antiepileptic drugs that interact with metabolic enzymes were associated with increased contraceptive failure rates. Measurement of conception in claims data had adequate accuracy to uncover a strong drug-drug interaction, offering promise for broader application in comparative effectiveness studies on hormonal contraceptives to inform clinical and regulatory decisionmaking.
BACKGROUND: Accurate estimation of conception is critical in the assessment of the effects of drugs used during pregnancy or to prevent pregnancy. In a novel application, we studied the effectiveness of oral contraceptives (OCs), where misclassification of conception relative to OC exposure may obscure effect estimates. METHODS: We studied OC failure, in a large claims database, among women who used antiepileptic drugs with metabolizing enzyme-inducing properties (carbamazepine or oxcarbazepine), which reduce OC's effectiveness or enzyme-neutral properties (lamotrigine or levetiracetam), with no expected impact on OC effectiveness. We compared conception rates in women 12-48 years of age concomitantly using OCs and enzyme-inducing drugs with rates in concomitant users of OCs and enzyme-neutral drugs. We measured conception with a validated algorithm that estimates gestational age based on pregnancy endpoints. We estimated relative and attributable risk using generalized estimating equation models after standardized mortality ratio weighting. RESULTS: We identified 89,777 concomitant use episodes with adjusted contraceptive failure rates of 1.6 (95% confidence interval (CI) = 1.4, 1.8) per 100 person-years among users of enzyme-neutral drugs and 18,964 episodes with a rate of 2.3 (1.9, 2.8) among users of enzyme-inducing drugs. The relative risk of conception for enzyme-inducing group was 1.4 (1.1, 1.8), and the rate difference was 0.7 (0.2, 1.2). CONCLUSIONS:OCs in combination with antiepileptic drugs that interact with metabolic enzymes were associated with increased contraceptive failure rates. Measurement of conception in claims data had adequate accuracy to uncover a strong drug-drug interaction, offering promise for broader application in comparative effectiveness studies on hormonal contraceptives to inform clinical and regulatory decisionmaking.
Authors: Joshua Brown; Tamra Goodrow; Dan Hartman; Justin L Hay; Kevin Hershberger; Susan Hershenson; Douglas McNair; Bethany Matthews; Mark A Milad; Stephan Schmidt; Kirsten M Vogelsong; Ping Zhao Journal: Contracept X Date: 2022-01-30